1. Field of the Invention
This invention relates to the synthesis and biological activity of a novel enkephalin analog. More particularly, this invention is concerned with the synthesis and biological activity of [D-Thr.sup.2, .DELTA..sup.3 Pro.sup.5 ]-enkephalinamide.
2. Description of the Prior Art
The enkephalinamide compound [D-Met.sup.2, Pro.sup.5 ]-enkephalinamide has been reported to be a potent analgesic agent by Bajusz et al., FEBS Letters 76,91 (1977).
It has been known in the art that proline can be replaced by thiazolidine-4-carboxylic acid (Thz) in biologically-active peptides. See, for example, Felix el al., Int. J. Pept. Prot. Res. 5, 201 (1973) and Rosamond and Ferger, J. Med. Chem. 19, 873 (1976).
Further, it is known that the 2-position in Met-enkephalin appears to be sensitive to the nature of the side chain. Hambrook et al., Nature (London) 262, 782 (1976); Pert et al., Science 194, 330 (1976); and Bajusz et al., Acta Biochim. Biophys. Acad. Sci., Hung. 11, 305 (1976).
Recently, Roemer et al., Nature 268, 547 (1977) have reported on several Met-enkephalin analogs, the most potent analgesic of the group being [D-Ala.sup.2, MePhe.sup.4, MetO.sup.5 -ol] enkephalin which was indicated to be orally active.
U.S. Patent No. 4,103,005 to Li describes the synthesis and biological activity of enkephalin analogs, [D-Met.sup.2, Thz.sup.5 ]-enkephalinamide and [D-Thr.sup.2, Thz.sup.5 ]-enkephalinamide, which are claimed to be potent analgesic agents. In accordance with the present invention, disclosed herein is [D-Thr.sup.2, .DELTA..sup.3 Pro.sup.5 ]-enkephalinamide, a potent agent for the inhibition of 5-hydroxytryptophan-induced diarrhea by intravenous injection.